Cancer treatment for people with PALB2 mutations

People with an inherited PALB2 mutation who have been diagnosed with cancer may have different treatment options than people without a mutation. To learn more about standard of care treatment options for specific types of cancer, visit our section on Cancer Treatment by Cancer Type. 

If you have an inherited PALB2 mutation, have been diagnosed with cancer and any of the situations below apply to you, you may want to speak to your doctor about your medical options. You may also consider enrolling in a clinical trial studying which treatments work best for people with an inherited PALB2 mutation. 

• You have metastatic prostate cancer
• You have advanced ovarian cancer
• You have advanced pancreatic cancer
• You have been diagnosed with breast cancer
• You are making breast cancer surgical decisions

PARP inhibitors

PARP inhibitors are a type of targeted therapy that work by blocking a protein used to repair damaged DNA. They were initially developed to treat cancers in people with an inherited BRCA1 or BRCA2 mutation. Since then, research and additional FDA approvals have expanded use of PARP inhibitors to more situations. People with a PALB2 mutation who have been diagnosed with cancer may want to ask their doctor about PARP inhibitor therapy. 

Metastatic prostate cancer

The PARP inhibitor, Lynparza (olaparib) has received FDA-approval to treat men with metastatic, castration-resistent prostate cancer, who have a mutation in PALB2 or another gene linked to a certain type of DNA damage repair. Lynparza may be used to treat men whose prostate cancer has progressed on enzalutamide (Xtandi) or abiraterone (Zytiga). 

PARP inhibitors for advanced ovarian, fallopian tube or primary peritoneal cancer

Several PARP inhibitors have been approved to treat ovarian cancers at different stages of the disease. In some situations, a tumor biomarker test known as an HRD test ("hemologous recombination deficiency") can help women with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from a PARP inhibitor. 

• Advanced cancer which has recurred after third-line treatment:
  • HRD testing can help women with an inherited PALB2 mutation and advanced ovarian cancer which has recurred after three lines of treatment learn if they may benefit from the PARP inhibitor Zejula (niraparib).
• Maintenance therapy after first-line treatment
  • HRD testing can help women with an inherited PALB2 mutation and advanced ovarian cancer learn if they may benefit from the PARP inhibitor Lynparza?(olaparib) in combination with bevacizumab as maintenance therapy after first-line platinum chemotherapy.
  • Zejula is approved for maintenance therapy in women with advanced ovarian, fallopian tube, or primary peritoneal cancer who had a complete or partial response to first-line platinum-based chemotherapy. Zejula for maintenance therapy does not require an HRD test. 
• Maintenance therapy after treatment of recurrent cancer
  • Zejula and Rubraca (rucaparib) are both approved for maintenance therapy in women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum based chemotherapy.

PARP inhibitors for pancreatic cancer

Although PARP inhibitors have not specifically received FDA approval to treat panceratic cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. The PARP inhibitor Lynparza is FDA approved for maintenance treatment of pancreatic cancer in people with a BRCA mutation whose disease has not progressed after completing first-line platinum-based chemotherapy.
 

PARP inhibitors for breast cancer

Although PARP inhibitors have not specifically received FDA approval to treat breast cancer in people with PALB2 mutations, the American Society of Medical Genetics released a paper suggesting that people with PALB2 mutations and cancer should be considered for the same treatments and clinical trials as people with a BRCA1 or BRCA2 mutation. Below are guidelines for PARP inhibitors for treating breast cancer in people with a BRCA1 or BRCA2 mutation. 

• Treatment for metastatic breast cancer: The PARP inhibitors, Lynparza (also known as olaparib) and Talzenna (also known as talazoparib) both have received FDA approval for treating metastatic breast cancer caused by a BRCA mutation.
• Treatment for early-stage breast cancer: Based on results from a large clinical trial, experts recommend one year of the PARP inhibitor olaparib for people with early-stage, HER2-negative breast cancer who have an inherited BRCA mutation and who are at high risk for recurrence.

Breast cancer surgical decisions 

Because of the high risk for a second breast cancer diagnosis, women who are diagnosed with breast cancer who test positive for an inherited mutation in PALB2 may choose bilateral mastectomy rather than lumpectomy and radiation. Mutation carriers who undergo mastectomy are less likely to develop a second breast cancer.